Search Results (47)

Recurrent brain tumors—including high-grade gliomas, brain metastases, and aggressive meningiomas—continue to carry a poor prognosis, with high mortality despite therapeutic advances. The aim of this narrative review is to summarize and critically discuss the current evidence on the role of intra-arterial radioligand therapy (RLT) in the treatment of recurrent brain tumors. RLT, a targeted form of radionuclide therapy, has gained increasing attention for its potential theranostic applications in neuro-oncology. A literature search was conducted using PubMed and Scopus, including clinical studies evaluating intra-arterial radioligand delivery in central nervous system tumors. Recent research has explored intra-arterial administration of radioligands targeting somatostatin receptors and prostate-specific membrane antigen (PSMA). Somatostatin receptors are overexpressed in meningiomas, while PSMA is highly expressed in the neovasculature of glioblastomas and brain metastases; both targets can be addressed using lutetium-177 (¹⁷⁷Lu)- or actinium-225 (²²⁵Ac)-labeled radiopharmaceuticals, traditionally delivered intravenously. Available evidence indicates that the intra-arterial route achieves markedly higher radionuclide uptake on ⁶⁸Ga-PSMA-11 and ⁶⁸Ga-DOTATOC PET, as well as increased absorbed doses in dosimetric models. Dosimetric analyses consistently show greater tracer accumulation compared with intravenous administration, without evidence of significant peri-procedural toxicity. Uptake in healthy brain tissue is minimal, and no relevant differences have been reported in liver or salivary gland accumulation between intra-arterial and intravenous RLT. Although based on heterogeneous and limited data, intra-arterial RLT appears to be a promising therapeutic strategy for recurrent brain tumors. Future research should focus on improving radioligand delivery beyond the blood–brain barrier and enhancing effective tumor targeting. Full article

Radiotherapy is a fundamental component in the management of head and neck malignancies, but its non-selective effects on surrounding normal tissues can result in significant oral complications. The oral cavity and oropharynx contain several radiosensitive structures, including mucosa, salivary glands, and alveolar bone, which are susceptible to both acute and late toxicities resulting in mucositis, xerostomia, and osteoradionecrosis. Although dentomaxillofacial diagnostic imaging, such as intraoral radiography, panoramic imaging and cone-beam computed tomography (CBCT), delivers radiation doses several orders of magnitude lower than therapeutic exposures, its biological impact on previously irradiated tissues remains underexplored. Even low-dose X-rays may act as secondary stressors, reactivating oxidative and inflammatory pathways in tissues with compromised repair capacity. In this review, we examine the radiobiological and dosimetric implications of using diagnostic ionizing imaging in patients undergoing or recently having completed head and neck radiotherapy. We summarize current evidence on potential additive effects of low-dose imaging, emphasizing the importance of justification, timing, and protocol optimization. Finally, we discuss radioprotective strategies (e.g., dose modulation, field limitation, and integration of modern low-dose imaging technologies) designed to reduce unnecessary exposure, thus enhancing tissue preservation and ensuring diagnostic safety in this vulnerable patient population Full article

Oral squamous cell carcinoma (SCC) is typically found in middle-aged or elderly individuals, is more common in men than women, can occur at any mucosal site, and is associated with a poor prognosis. The primary risk factors for oral SCC include the use of tobacco, betel nut, or areca nut, and excessive alcohol consumption. A comprehensive management plan for oral SCC typically involves a multidisciplinary team approach with surgery being the primary treatment approach, with or without radiotherapy. Radiotherapy is an essential component in the management of oral SCC, with its application guided by both tumour- and patient-related factors. It may be employed as a definitive, adjuvant, or palliative modality, depending on tumour stage, resectability, surgical margins, histopathological characteristics, as well as the patient’s overall health, financial considerations, and personal preferences. Effective radiotherapy for oral SCC inevitably leads to various tissue toxicities, which can vary among patients. These variations are primarily influenced by patient-specific characteristics, tumour-specific factors, and aspects related to the radiotherapy itself. Some of the complications resulting from ionizing radiation (IR) include oral mucositis, facial dermatitis, salivary gland dysfunction, trismus, and osteoradionecrosis, along with their management strategies. Full article

Background: Radiation-induced salivary gland (SG) hypofunction is mediated via microvascular dysfunction and radical oxygen species. N-acetylcysteine amide (NACA) has shown antioxidant properties with low toxicity. We explored NACA’s potential as a radioprotector of SG function. Methods: Bovine aortic endothelial cells (BAECs) were treated with NACA before irradiation with a single 10 Gy dose. Apoptosis was assessed by bis-benzimide staining and quantified via fluorescence microscopy. In vivo, NACA was administered to mice prior to a single 15 Gy head and neck irradiation. Eight weeks post-irradiation, saliva production was measured using pilocarpine stimulation; lysozyme levels were analyzed by ELISA. SGs were collected for immunohistochemistry. Results: BAEC apoptosis was substantially lower in NACA-treated cells vs. radiation-only (10% vs. 23%). In vivo, mice lost significant weight and developed severe hair loss eight weeks post-irradiation—attenuated by NACA pretreatment. Saliva production was reduced by 72% post-radiation, with a corresponding drop in lysozyme. NACA increased salivary flow by 42% and prevented lysozyme reduction. Post-radiation decline in microvessel density was also prevented by NACA. Conclusions: These outcomes suggest NACA may serve as a radioprotector of SG function in patients undergoing radiotherapy for head and neck cancer. Full article

Targeted alpha therapy (TAT) has recently emerged as a highly promising approach for the management of metastatic castration-resistant prostate cancer (mCRPC), especially in patients with disease progression despite standard treatments. Among alpha-emitter radiopharmaceuticals, actinium-225-labelled prostate-specific membrane antigen ([225Ac]Ac-PSMA) has shown remarkable potential due to its high linear energy transfer (LET), short path length, and ability to induce potent, localised cytotoxic effects. This review summarises current clinical evidence regarding [225Ac]Ac-PSMA radioligand therapy (RLT), emphasising its efficacy, safety profile, and position relative to beta-emitter therapy with lutetium-177 ([177Lu]Lu-PSMA). Data from compassionate-use programs and small clinical trials demonstrate that [225Ac]Ac-PSMA produces significant biochemical and imaging responses, including > 50% declines in prostate-specific antigen (PSA) and lesion regression on [68Ga]Ga-PSMA PET/CT, even in heavily pre-treated mCRPC cohorts. Xerostomia, renal toxicity, and haematological adverse effects remain the main safety challenges, necessitating optimisation of patient selection, dosing strategies, and salivary gland protection protocols. Compared with [177Lu]Lu-PSMA, [225Ac]Ac-PSMA appears effective even in cases of beta-refractory disease, highlighting its complementary role rather than a competitive alternative. However, limited availability, high production costs, and the lack of large-scale, randomised trials hinder widespread clinical adoption. Future directions include combination protocols, improved radiopharmaceutical design, and trials evaluating its use in earlier disease stages. This review provides a comprehensive overview of the clinical aspects of [225Ac]Ac-PSMA RLT and its evolving role in advanced prostate cancer management. Full article

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Head and neck cancer encompasses a diverse group of malignant neoplasms originating in regions such as the oral cavity, oropharynx, hypopharynx, larynx, sinonasal cavities, and salivary glands. HNC represents a significant public health challenge, and recent reports indicate an increment in the incidence of HNC in young adults. In 2020, approximately 377,700 new HNC cases and 177,800 HNC-related deaths were reported globally. Major risk factors include tobacco smoking, alcohol consumption, and human papillomavirus (HPV) infections. HNC impacts vital functions such as breathing, swallowing, and speech. Treatments for this type of cancer within this complex anatomy include surgery, radiotherapy, and chemotherapy combinations. Radiotherapy is often an essential component of both curative and palliative HNC treatment, balancing tumor control with the preservation of function and appearance. However, its use can damage adjacent normal tissues, causing acute or chronic toxicity. One complication of HNC irradiation is VF fibrosis, which leads to severe voice impairments, significantly affecting patients’ quality of life. Fibrosis involves excessive and aberrant deposition of extracellular matrix, driven by factors such as TGF-β1 and inflammatory cytokines, which ultimately impair the flexibility and function of VF. Current radiation-induced fibrosis treatments primarily focus on symptom management and include systemic therapies like corticosteroids, anti-inflammatory drugs, and antioxidants. However, these treatments have limited efficacy. Experimental approaches targeting molecular pathways involved in fibrosis are being explored. Given the limitations of these treatments, advancing research is crucial to develop more effective therapeutic strategies that can significantly improve the quality of life for HNC patients, especially those vulnerable to VF fibrosis. Full article

This review systematically examines the oral complications associated with conventional and novel anti-cancer therapies. It highlights that while molecularly targeted agents including monoclonal antibodies targeting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, tyrosine kinase inhibitors, and immune checkpoint inhibitors tend to exhibit a lower overall toxicity profile compared to traditional cytotoxic chemotherapeutics, they are nonetheless linked to significant oral adverse events. These complications encompass inflammatory mucosal reactions known as mucositis, salivary gland dysfunction leading to a sensation of dryness in the mouth, taste alterations referred to as dysgeusia, and, critically, medication-related osteonecrosis of the jaw. In particular, bone-modifying agents such as bisphosphonates and denosumab disrupt bone remodeling and the formation of new blood vessels, thereby increasing the susceptibility to osteonecrosis of the jaw, especially following invasive dental procedures. The review delineates the multifactorial pathogenesis underlying these toxicities, which involves direct cell toxicity, impaired wound healing, and secondary infections. Furthermore, it emphasizes the importance of pre-treatment dental evaluation and preventive strategies including patient education, prophylactic dental care, and the integration of adjunctive therapies such as laser therapy and autologous platelet concentrates to mitigate these adverse effects. The analysis advocates for interdisciplinary collaboration between oncologists and dental professionals to optimize management protocols, enhance treatment adherence, and ultimately improve the quality of life for oncology patients undergoing anti-cancer therapy. Full article

This study aims to retrospectively assess the safety of [²²⁵Ac]Ac-PSMA-PRLT, both as monotherapy and in combination (TANDEM) with Lutetium-177, concerning tolerance after the radiopharmaceutical administration and long-term safety, its impact on salivary glands’ function, overall survival (OS), and follow-up duration. Between December 2020 and September 2024, 89 patients received a total of 151 cycles of [²²⁵Ac]Ac-PSMA-PRLT. Patients with at least one follow-up (n = 71) were included in the analysis to evaluate xerostomia, as well as long-term hematological, renal, and hepatic toxicities, graded according to CTCAE v5.0. The most common adverse event after the radiopharmaceutical administration was flare pain (n = 16). As of the time of analysis, 68 patients had passed away (76.4%; range of survival 5 days to 39 months, median 7 months), while 21 patients were still alive (23.6%; follow-up duration: 1–33 months). Severe (G3/G4) long-term adverse events were rare, with 15 cases of G3 anemia (21.1%), 6 cases of G3 leukocytopenia (8.4%), and 14 cases of G3/G4 thrombocytopenia (19.7%). Hematological toxicity was primarily associated with severe bone marrow involvement or prior chemotherapy. Additionally, one case of G3 nephrotoxicity (1.4%) and six cases of G3 hepatotoxicity (8.4%) were observed. Only nine patients (12.7%) reported de novo xerostomia (G1/G2). In conclusion, this study demonstrates that [²²⁵Ac]Ac-PSMA PRLT, both as monotherapy and combined with [¹⁷⁷Lu]Lu-PSMA as TANDEM PRLT, is generally safe in terms of both tolerance after the radiopharmaceutical administration and long-term toxicity. Full article

Inwardly rectifying potassium (Kir) channels regulate essential physiological processes in insects and have been identified as potential targets for developing new insecticides. Flonicamid has been reported to inhibit Kir channels, disrupting the functions of salivary glands and renal tubules. However, the precise molecular target of flonicamid remains debated. It is unclear whether flonicamid directly targets Kir channels or acts on other sites involved in the activation of transient receptor potential vanilloid (TRPV) channels. In this study, we observed that flonicamid is more toxic to flies than its metabolite, flumetnicam. This higher toxicity is difficult to reconcile if nicotinamidase is the active target, as flonicamid does not inhibit nicotinamidase. An alternative explanation is that flonicamid and flumetnicam may have distinct targets or act on multiple targets. Furthermore, reducing the expression of three individual Kir genes in the salivary glands of D. melanogaster significantly decreased the flies’ susceptibility to both flonicamid and flumetnicam. The double knockdown of Kir1 with Kir3 or Kir2 with Kir3 further reduced the flies’ sensitivity to both compounds. These findings confirm the involvement of Kir channels in mediating the toxic effects of flonicamid on flies. Overall, this study offers new insights into the physiological roles of insect Kir channels and flonicamid toxicity. Full article

Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors’ quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes. Full article

Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan–Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0–47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group. Full article

Purpose: To investigate the impact of physiologically based pharmacokinetic (PBPK) parameters on physical, biological, and statistical measures in lutetium-177-labeled radiopharmaceutical therapies (RPTs) targeting the prostate-specific membrane antigen (PSMA). Methods: Using a clinically validated PBPK model, realistic time–activity curves (TACs) for tumors, salivary glands, and kidneys were generated based on various model parameters. These TACs were used to calculate the area-under-the-TAC (AUC), dose, biologically effective dose (BED), and figure-of-merit BED (fBED). The effects of these parameters on radiobiological, pharmacokinetic, time, and statistical features were assessed. Results: Manipulating PBPK parameters significantly influenced AUC, dose, BED, and fBED outcomes across four different BED models. Higher association rates increased AUC, dose, and BED values for tumors, with minimal impact on non-target organs. Increased internalization rates reduced AUC and dose for tumors and kidneys. Higher serum protein-binding rates decreased AUC and dose for all tissues. Elevated tumor receptor density and ligand amounts enhanced uptake and effectiveness in tumors. Larger tumor volumes required dosimetry adjustments to maintain efficacy. Setting the tumor release rate to zero intensified the impact of association and internalization rates, enhancing tumor targeting while minimizing the effects on salivary glands and kidneys. Conclusions: Optimizing PBPK parameters can enhance the efficacy of lutetium-177-labeled RPTs targeting PSMA, providing insights for personalized and effective treatment regimens to minimize toxicity and improve therapeutic outcomes. Full article

Objectives: Oral diseases are among the most prevalent diseases globally. Accumulating new evidence suggests considerable benefits of epigallocatechin-3-gallate (EGCG) for oral health. This review aims to explore the role and application of EGCG in main oral diseases. Methods: This narrative review thoroughly examines and summarizes the most recent literature available in scientific databases (PubMed, Web of Science, Scopus, and Google Scholar) reporting advances in the role and application of EGCG within the dental field. The major keywords used included “EGCG”, “green tea extract”, “oral health”, “caries”, “pulpitis”, “periapical disease”, “periodontal disease”, “oral mucosa”, “salivary gland”, and “oral cancer”. Conclusions: EGCG prevents and manages various oral diseases through its antibacterial, anti-inflammatory, antioxidant, and antitumor properties. Compared to traditional treatments, EGCG generally exhibits lower tissue irritation and positive synergistic effects when combined with other therapies. Novel delivery systems or chemical modifications can significantly enhance EGCG’s bioavailability, prolong its action, and reduce toxicity, which are current hotspots in developing new materials. Clinical significance: this review provides an exhaustive overview of the biological activities of EGCG to major oral diseases, alongside an exploration of applications and limitations, which serves as a reference for preventing and managing oral ailments. Full article